Marijuana abuse directly affects society in terms of deleterious health consequences. As such, the development of medications to treat marijuana abuse is of utmost importance. Cannabinoid drug discrimination is a model of marijuana intoxication. Although both exogenous and endogenous cannabinoids exist, differences have been found between them. Understanding these differences are essential in determining the role of CB1 cannabinoid receptors in the effects of cannabinoids. This study will explore cannabinoid discrimination using the exogenous cannabinoid delta 9-tetrahydrocannabinol and the endogenous cannabinoid methanandamide in mice lacking CB1 cannabinoid receptors (CB1 null mutant mice) and their wild type littermates (CB1 receptors present). CB1 null mutant mice and wild type mice will be trained to discriminate delta 9-THC or methanandamide from vehicle. Mice will be trained to press one lever following administration of delta 9-THC or methanandamide and to press another lever after vehicle injection according to a fixed-ratio (FR) 10 schedule of liquid reinforcement. Daily 15-minute training sessions will be held Monday-Friday until the mice have met two criteria during 8 of 10 consecutive sessions: (1) the first completed FR-10 is on the correct lever and (2) > 80 percent of the total responding occur on the correct lever. When the two criteria are met, substitution tests with cannabinoid and non-cannabinoid compounds will be conducted. These 15-minute test sessions will be held on Tuesdays and Fridays. Antagonism tests with SR141716A, the selective CB1 cannabinoid receptor antagonist, and SR144528, the selective CB2 cannabinoid receptor antagonist, will also be conducted. Results from this study will provide insight into possible non-CB1, non-CB2 mechanisms of action for endogenous cannabiniods.
| Baskfield, Cassandra Y; Martin, Billy R; Wiley, Jenny L (2004) Differential effects of delta9-tetrahydrocannabinol and methanandamide in CB1 knockout and wild-type mice. J Pharmacol Exp Ther 309:86-91 |
